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Viruses normally seem like evil little germs; they often invade our bodies’ cells and hijack their inner machinery to mass produce viral invaders, which eventually destroy their host cells as they bust out to besiege more cells. The process repeats ad nauseam. But what if that wicked master plan could be twisted to do our bidding? What if viruses only invaded cells we wanted them to kill—like cancer cells?

Researchers got the initial idea of using viruses decades ago (PDF) and racked up a number of enticing anecdotes that suggested the idea could work. After all, cancer cells, in their altered state that allows them to replicate quickly and uncontrollably, often shut off their anti-viral defenses and are prone to infection. But scientists’ attempts at training viruses to be cancer assassins fell short in bigger trials—until now.

On Tuesday, the Food and Drug Administration approved the first viral-based cancer therapy. The virus, called talimogene laherparepvec (T-VEC), is a genetically engineered herpes simplex virus that can help treat advanced melanoma. Its genetic tweaks make it incapable of usurping normal, healthy cells. Thus, it doesn’t cause herpes. But when it meets cancer cells, it initiates cellular carnage. The virus is also engineered to carry a gene encoding the GM-CSF protein, which triggers the immune system. As the virus ravages cancer cells, GM-CSF gets released, boosting a patient’s natural defenses.

So far, T-VEC isn’t a wonder drug, but it’s helpful. In a large clinical trial published in May in the Journal of Clinical Oncology, researchers found that the virus shrank tumors and extended patient survival by a median of 4.4 months. The results were just shy of showing a statistically significant benefit to overall health. Still, the researchers are hopeful that when the viral therapy is combined with traditional therapies, it could significantly boost survival rates in patients.

And with T-VEC’s approval, researchers see a clear path for more viral-based remedies. Many such therapies are already in the works, and researchers are combing through the large varieties of viruses for the next potential cancer slayer.

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I currently work on this program--there's some interesting combination therapies for a variety of different tumor sites that are suggesting substantially improved response rates compared to using just one of the therapies alone. Expect to see initial read outs of these new trials in the next 2 years or so.

And with T-VEC’s approval, researchers see a clear path for more viral-based remedies. Many such therapies are already in the works and researchers are combing through the large varieties of viruses for the next potential cancer slayer.

I think this is perhaps the best news I've read on the cancer front in a very long time.

Great job!

Yours for only $126,222.15 per treatment!Oh, and not covered by insurance, of course.

Oh you Americans are adorable with your price on health and non-universal insurance!

I wonder why it's not as effective as it's expected to be. The cancer cells can't detect it, so what's the problem?

I am not familiar with the exact mechanism of action in this case, but in general targeted therapies are never 100% effective because tumors are heterogeneous populations. In order to selectively kill, the therapy must target some feature that is present in the cancer, but not normal cells (often a aberrant protein or receptor). Tumor cells that lack this feature or express it in a different way would be able to evade destruction.

Also, the resistant populations will multiply and same treatment is less likely to work the second time around. (evolution at work)

I'm not clear on what mechanism allows T-VEC to replicate in melanoma cells and not "normal" cells. Would appreciate if anyone could learn me on that.

How have I gotten this far into the comments and not seen anything about the T-Virus....

Hey, I posted about it! At least the T-cell infecting chimeric treatment that was being tested for CLL! I'm honestly curious to hear about this research as it sounds like a similar, but different approach and I'd like to understand those differences.

Who said anything about a cure? That's a superlative a lot of people seem to add on themselves when reading about this kind of research. (And the carnage part is not a quote from the researchers)

This is how cancer research usually goes; a lot of incremental improvements. Big silver bullet type treatments are few and far between.

Being a researcher myself who's currently working in a medical field, and *not* being a total fucking idiot myself, I know this. It's quality of life during those additional 4.4 months that's critical here. Having seen first hand what severe cancers do to people, the question is often "Do they really want to live an extra few months in (often) severe pain or discomfort 24/7?"

The quality of life issue is getting danced around here quite majorly.

I'd also add I didn't see a mention of T-cell recruitment like in Dr. Porter's work. They added CD137 and CD3-zeta expression to encourage recruitment, but here I only see CSF2 mentioned. One of the neat parts of Dr. Porter's work is that it retargetted T-cells so they could recognize CD19 expression.

No, no, no! You do not mix viri and T-cells. We don't need a zombie apocalypse just as we begin to solve cancer.

There is a warning against using with people with reduced immune response.

It is injected directly into tumors, rather than delivered throughout the body intravenously.

The limited efficacy has only been shown for skin and lymph node lesions, not for other metastatic lesions.

Side effects were rather limited, especially in comparison to traditional cancer treatments.

Also, note that melanoma is one of the cancers that has been most resistant to effective treatments, and the treatments that can be partially effective have side effects which are often severely debilitating. For that disease, an extra 4.4 months with limited side effects is actually a huge step forward (assuming that stat holds up in wider usage, of course).

EDIT: Hell, even if you get the same life expectancy as with other treatments, but with much lower side effects, even that would be a big step forward, considering the side effect experience of most melanoma patients.

And with T-VEC’s approval, researchers see a clear path for more viral-based remedies. Many such therapies are already in the works and researchers are combing through the large varieties of viruses for the next potential cancer slayer.

I think this is perhaps the best news I've read on the cancer front in a very long time.

Great job!

Yours for only $126,222.15 per treatment!Oh, and not covered by insurance, of course.

The problem is a pharmacokinetic one. Once the bacon is fully fried, in about 1.5 hours, it loses effectiveness due to extremely high oral bioavailability. Reapplication is difficult as the smell of bacon tends to attract large numbers of land sharks.

I wonder why it's not as effective as it's expected to be. The cancer cells can't detect it, so what's the problem?

I am not familiar with the exact mechanism of action in this case, but in general targeted therapies are never 100% effective because tumors are heterogeneous populations. In order to selectively kill, the therapy must target some feature that is present in the cancer, but not normal cells (often a aberrant protein or receptor). Tumor cells that lack this feature or express it in a different way would be able to evade destruction.

Also, the resistant populations will multiply and same treatment is less likely to work the second time around. (evolution at work)

I'm not clear on what mechanism allows T-VEC to replicate in melanoma cells and not "normal" cells. Would appreciate if anyone could learn me on that.

I am not sure of the exact mechanism of this vector, but the usual trick is to ensure that the virus is missing genes to neutralize p53 or RB, proteins which prevent the the cell from making DNA-replicating proteins (moving through G1 phase) . One or more of these proteins are naturally missing in the tumor cells, so the deficient virus can replicate in these cells, but not in normal cells. Some tumor cells may have no defect in either of the targeted genes, in which case the virus cannot replicate in them, and the cells are unaffected by the therapy.

Only four months?..... Sounds meager until you are the one with cancer. Also it is a first iteration. Future advances would seem to be likely.

And of course the 4 and a half months is just an average - you have people for whom the treatment is not successful, who don't get much extra time if at all, but there are others who might get a couple years out of it.

On top of that, even if it didn't give you any more time, you have quality of life - this course of treatment probably has negligible side-effects compared to the terrible effects of most chemo treatments. Even if it only allows you to cut back on the chemo dosing, it could be worth it.

Who said anything about a cure? That's a superlative a lot of people seem to add on themselves when reading about this kind of research. (And the carnage part is not a quote from the researchers)

This is how cancer research usually goes; a lot of incremental improvements. Big silver bullet type treatments are few and far between.

Being a researcher myself who's currently working in a medical field, and *not* being a total fucking idiot myself, I know this. It's quality of life during those additional 4.4 months that's critical here. Having seen first hand what severe cancers do to people, the question is often "Do they really want to live an extra few months in (often) severe pain or discomfort 24/7?"

The quality of life issue is getting danced around here quite majorly.

Read the NYT Magazine article from about 10 years ago on starvation therapy for Type I diabetes, and what happened when insulin appeared. The kids who had survived the truly horrendous starvation regime, (maximum life extension about 5 years; QOL abysmal) lived up to 70 years on insulin therapy; QOL excellent. One needs to look at the whole picture, which may not be got from simple extrapolations of what currently is. Every journey starts with a single step.

I'm sure I read something a while ago that researchers were quite confident that a virus packed with a nasty payload had some of its external chemistry altered to target very specific rapidly multiplying cells - something that *all* cancers have in common, and it was starting to look very effective. Unfortunately there was also one other type of cell that exhibits the same property - the placenta.

I'm sure I read something a while ago that researchers were quite confident that a virus packed with a nasty payload had some of its external chemistry altered to target very specific rapidly multiplying cells - something that *all* cancers have in common, and it was starting to look very effective. Unfortunately there was also one other type of cell that exhibits the same property - the placenta.

Anyone else see that one?

You are not targeting rapidly dividing cells, but cells deficient in cell cycle control, which is not a description of placental cells. Besides which, a woman with a melanoma serious enough to require this type of therapy is already likely to have had therapies which would terminate any pregnancy. Therapy tends to exist in a context of real worlds, not theoretical ones.

This is very interesting work indeed. Note that the control group here is also recieving GM-CSF (aka CSF2) via subQ.

Generally speaking GM-CSF induces the proliferation of granulocytic (neutrophils, basophils, eosiniphils) and monocytic (monocytes/macrophages, some dendritic cells) precursors in the bone marrow. The latter cells in particular are extremely important generators of Reactive Oxygen Species, and for the purposes here, Tumor Necrosis Factor, which can kill cancer cells directly, and also induces the aforementioned neutrophils to release TRAIL, which could also be helpful, depending upon tumor type.

Note that macrophages (and especially DCs) are important Antigen Presenting Cells, with antigen presentation being a prerequisite to the actions of the crucial Helper T (generally CD4+) and (especially notable in cancer) Cytotoxic T cells (gen. CD8+). Perhaps most importantly for things like melanoma (and antigen presentation generally), dendritic cells, the super-presenters (from the myeloid derived side at least) are going to be stimulated, kicking tumor-specific cytotoxic T cell activation and proliferation into seriously high gear.

For localized antitumor activity (thus probably part of the difference between SubQ GM-CSF treatment and infection of the tumor with a GM-CSF producing modified virus, albeit less than DC activation), neutrophils in particular can migrate up a GM-CSF gradient and probably help to recruit monocytes once there.

All of this is in addition to the directly oncolytic activity of the recombinant virus itself! The success here seems an extremely promising start for the treatment of other inoperable tumor types. The virus is of course deliberately attenuated, but could cause problems in immunocompromised patients, and thus the warnings.

This is early work, but even the 'limited' success seen here (all things considered) is impressive!

And with T-VEC’s approval, researchers see a clear path for more viral-based remedies. Many such therapies are already in the works and researchers are combing through the large varieties of viruses for the next potential cancer slayer.

I think this is perhaps the best news I've read on the cancer front in a very long time.

Great job!

Yours for only $126,222.15 per treatment!Oh, and not covered by insurance, of course.

pppfffft....

That's not even the highest "list price" for a covered cancer treatment.

From what I understand this virus is genetically modified; engineered. Really no different from GMO food sources.

With public opinion of GMO based food going down (due to pseudo-science or real science, I can't tell) I wonder what opinion (public or expert) will be given to this virus based treatment.

Is this not the premise of I Am Legend?

Then refuse treatment. Then we can get the anti-science crowd out of the population at a slightly faster rate.

Maybe we can publish an article about how bad this technology is in some of the more egregious pseudoscience rags to get the attrition rate to ratchet up another notch.

This is a dangerous path to be treading and no one should try to minimize this fact. Your "science uber alles" mentality is really no better. One key problem with genetic meddling of food crops is that you by definition have to "let the genie out of the bottle" and contaminate the entire environment.

The virus, called talimogene laherparepvec (T-VEC), is a genetically engineered herpes simplex virus that can help treat advanced melanoma. Its genetic tweaks make it incapable of usurping normal, healthy cells. Thus, it doesn’t cause herpes. But when it meets cancer cells, it initiates cellular carnage. The virus is also engineered to carry a gene encoding the GM-CSF protein, which triggers the immune system. As the virus ravages cancer cells, GM-CSF gets released, boosting a patient’s natural defenses.

Wonderful, descriptive prose.

I thought it was rather hyperbolic, personally. "Cellular carnage" against cancer cells sounds great, until you read that it extended life by 4.4 months and is thus nowhere near being a real cure. Many researchers are very guilty of using superlatives when they aren't really warranted.

As one for whom this kind of therapy is actually relevant, I agree. 4 extra months is nice but it's nowhere close to a cure. It's more accurate to view it as tentative baby steps.

And with T-VEC’s approval, researchers see a clear path for more viral-based remedies. Many such therapies are already in the works and researchers are combing through the large varieties of viruses for the next potential cancer slayer.

I think this is perhaps the best news I've read on the cancer front in a very long time.

Great job!

Yours for only $126,222.15 per treatment!Oh, and not covered by insurance, of course.

Oh you Americans are adorable with your price on health and non-universal insurance!

Except Europeans "ration" this kind of stuff. Drugs that are covered in the US aren't in other European countries. Coverage might suddenly stop when the budget runs out. Restrictions on expensive therapies are tighter. Even basic diagnostics seem to be in short supply despite the fact that you should be cutting out the middleman and making things cheaper.

If anything the American system is MORE likely to be aggressive saving your life. Plus this stuff is being developed here.

And with T-VEC’s approval, researchers see a clear path for more viral-based remedies. Many such therapies are already in the works and researchers are combing through the large varieties of viruses for the next potential cancer slayer.

I think this is perhaps the best news I've read on the cancer front in a very long time.

Great job!

Yours for only $126,222.15 per treatment!Oh, and not covered by insurance, of course.

Only in the US.

It will cost $20 in the rest of the world.

So we pay to save the rest of the world. I'm down with that. Someone has to take care of business. If it's not us, then the alternative is sending people to hospice care.

It's better than blowing it on another aircraft carrier.

I just love how eurotrash love to brag about stiffing the people doing the R&D.

I'm sure I read something a while ago that researchers were quite confident that a virus packed with a nasty payload had some of its external chemistry altered to target very specific rapidly multiplying cells - something that *all* cancers have in common, and it was starting to look very effective. Unfortunately there was also one other type of cell that exhibits the same property - the placenta.

Anyone else see that one?

Chemo already does this with the side effect of also destroying other rapidly multiplying cells that aren't cancer. This is why chemo patients go bald. Your bone marrow and GI tract also fall into this category.

Not all cancers have the same unregulated growth mechanism. Even targeting some of those individual growth mechanisms is a tricky business and doesn't always work or wears off over time.

There is a warning against using with people with reduced immune response.

It is injected directly into tumors, rather than delivered throughout the body intravenously.

The limited efficacy has only been shown for skin and lymph node lesions, not for other metastatic lesions.

Side effects were rather limited, especially in comparison to traditional cancer treatments.

Also, note that melanoma is one of the cancers that has been most resistant to effective treatments, and the treatments that can be partially effective have side effects which are often severely debilitating. For that disease, an extra 4.4 months with limited side effects is actually a huge step forward (assuming that stat holds up in wider usage, of course).

EDIT: Hell, even if you get the same life expectancy as with other treatments, but with much lower side effects, even that would be a big step forward, considering the side effect experience of most melanoma patients.

The remission stats were a lot more impressive than the survival, but given that intra- and peri- tumour injections of regular GM-CSF are a thing, the decision to go for unblinded injection of subcutaneous treatment in the controls rather than at least single-blinded direct injection was....odd.

And with T-VEC’s approval, researchers see a clear path for more viral-based remedies. Many such therapies are already in the works and researchers are combing through the large varieties of viruses for the next potential cancer slayer.

I think this is perhaps the best news I've read on the cancer front in a very long time.

Great job!

Yours for only $126,222.15 per treatment!Oh, and not covered by insurance, of course.

Oh you Americans are adorable with your price on health and non-universal insurance!

Except Europeans "ration" this kind of stuff. Drugs that are covered in the US aren't in other European countries. Coverage might suddenly stop when the budget runs out. Restrictions on expensive therapies are tighter. Even basic diagnostics seem to be in short supply despite the fact that you should be cutting out the middleman and making things cheaper.

If anything the American system is MORE likely to be aggressive saving your life. Plus this stuff is being developed here.

The American system is generally agreed to be at least twice as expensive per capita, and has worse disease outcomes than e.g. the UK. The US has great innovation, but terrible results.